Myasthenia gravis and Lambert-Eaton syndrome
An algorithmic testing approach to expediate diagnosis and treatment
Mayo Clinic-led research supports an optimized diagnostic approach that incorporates clinically relevant autoantibody profiles to screen for and confirm the presence of myasthenia gravis (MG) and Lambert-Eaton syndrome (LES).
Our first-line MG and LES evaluation examines levels of acetylcholine receptor binding antibodies (AChR-Bi). If positive, confirmatory testing measures levels of acetylcholine receptor modulating antibodies (AChR-Mo). In cases where AChR-Bi antibodies are not found, testing automatically reflexes to muscle-specific kinase (MuSK) antibody testing. This test enables the highest testing sensitivity by providing the lowest cut-off values of receptor binding antibodies.
Myasthenia gravis and Lambert-Eaton syndrome Test menu
Myasthenia gravis and Lambert-Eaton syndrome
Mayo Clinic research has advanced the science of testing for MG by demonstrating, through peer-reviewed and validated research, that an algorithmic testing approach involving automatic reflex to confirmatory testing for seropositive patients improves diagnostic accuracy. In addition, Mayo Clinic research has revealed that tests for certain biomarkers traditionally used to inform diagnosis lack utility. As a result, these nonactionable antibodies have been excluded from our assays.
- Commercially available LRP4-IgG assays may lack diagnostic value in seronegative clinical-electrodiagnostic (EDX)-confirmed MG.
- Striational antibody tests lack the sensitivity and specificity to predict malignancy or neurological phenotype.
- N-type voltage gated calcium channel (VGCC) antibodies are nonspecific and enable an increased chance of false positives.
Key testing
- MGMR | Myasthenia Gravis Evaluation with Muscle-Specific Kinase (MuSK) Reflex, Serum
- MGLE | Myasthenia Gravis/Lambert-Eaton Myasthenic Syndrome Evaluation, Serum
Advantages
- Provides higher specificity, sensitivity, and fewer false positives.
- Minimizes avoidable CT scans.
- Reduces unnecessary thymectomy and immunotherapy.
- Decreases cost and turnaround time by eliminating unnecessary testing.
Highlights
In this month’s episode of Lab Medicine Rounds, Justin Kreuter, M.D., interviews Jeffrey Winters, M.D., the medical director of the Therapeutic Apheresis Treatment Unit at Mayo Clinic for Myasthenia Gravis Awareness Month.
Divyanshu Dubey, M.B.B.S., explains how Mayo Clinic Laboratories' unique PDE10A and TRIM46 tests facilitate the management of central nervous system disorders triggered by cancers. Early diagnosis and treatment are important for managing disabling neurological symptoms and malignancy.
Advanced testing at Mayo Clinic Laboratories that confirmed a diagnosis of myasthenia gravis put Lorinda McKinley on the road to renewed health after she nearly lost it all to the rare autoimmune disease.
Christopher Klein, M.D., discusses Mayo Clinic’s updated myasthenia gravis and Lambert-Eaton syndrome testing approach. Automatic reflex to second-line testing saves time and increases sensitivity and specificity to confirm diagnosis in patients with atypical presentation.
References
- Klein CJ, Beecher G, Lamb C, Naddaf E, Milone M, Liewluck T, Dubey D, Zekeridou A, Shelly S, Mills JR. LRP4-IgG service line testing in seronegative myasthenia gravis and controls. J Neuroimmunol. 2022 Jul 15;368:577895. doi:10.1016/j.jneuroim.2022.577895. Epub 2022 May 18. PMID: 35617719.
- Shelly S, Mills JR, Dubey D, McKeon A, Zekeridou A, Pittock SJ, Harper CM, Naddaf E, Milone M, Mandrekar J, Klein CJ. Clinical utility of striational antibodies in paraneoplastic and myasthenia gravis paraneoplastic panels. Neurology. 2021 Jun 14;96(24):e2966-e2976. doi:10.1212/WNL.0000000000012050. PMID: 33903199.
- Zalewski NL, Lennon VA, Lachance DH, Klein CJ, Pittock SJ, Mckeon A. P/Q- and N-type calcium-channel antibodies: Oncological, neurological, and serological accompaniments. Muscle Nerve. 2016 Aug;54(2):220-7. doi:10.1002/mus.25027. Epub 2016 Feb 8. PMID: 26789908; PMCID: PMC4940238.